[unreadable] [unreadable] As evidenced by this application for a CDA (K08), the candidate desires to obtain expertise in molecular genetics, and to apply this expertise to the investigation of scoliosis. As a pediatric orthopaedist with a strong interest in the molecular genetics of pediatric musculoskeletal disorders, the candidate has begun genetic investigations of idiopathic scoliosis and clubfoot. He joined the faculty as a clinician-scientist and is in a position, with the support of this award, to move toward independent investigations into the molecular genetic basis of these disorders. Adolescent idiopathic scoliosis (AIS) is a highly prevalent condition affecting 2-3% of the adolescent population. Although the specific cause has not been established, there is strong evidence that genetic factors play a role. Isolating the gene(s) responsible for AIS will start a chain of scientific events with significant implications for both public health and healthcare spending. Annually, screening for this condition costs the national healthcare system over $56 million dollars, and over $180 million for AIS surgery, of which $48 million was charged to Medicaid. Recent work provides evidence for linkage of AIS to chromosome 16 (as reported by Miller et al.); the same area of linkage was found in a large pedigree evaluated in our laboratory (Lod score 3.17). The goal of this proposal is to better define this chromosomal region and to evaluate candidate genes in an effort to identify an AlS-disease gene. In order to maximize the likelihood of success and to provide for a variety of training experiences, two complementary approaches are proposed: 1) detailed characterization of the region of interest by high-density marker genotyping, and the use of gene annotation information for candidate gene mutation analysis. This work will be supported by our high-throughput sequencing and screening capabilities, state-of-the-art Center for Bioinformatics and Computational Biology, and the Center for Statistical Genetics Research. The candidate will be mentored by a Howard Hughes geneticist at the University of Iowa, and secondarily by recognized experts in statistical genetics, genetic computational bioinformatics, through a rigorous, well-organized series of didactic coursework. Together, the training plan and research proposal provide for a breadth of training, the potential for meaningful discovery, and support for the establishment of an independent research career. [unreadable] [unreadable] [unreadable] [unreadable]